The present invention relates to novel methods, combinations and compositions for reducing gastric bleeding during aspirin therapy in the treatment of inflammation. More particularly, the invention relates to methods, combinations and compositions therefor, of reducing gastric bleeding frequently found attendant to aspirin therapy in mammalian subjects which comprises administering in combination with aspirin, an effective amount of certain phenylalkylamines and phenylalkylureas.
There are various diseases in chronic and acute form which afflict mammals and for which aspirin therapy is indicated and prescribed. In many instances a high incidence of bleeding and ulceration results as side effects from the administration of aspirin for its anti-inflammatory effect. For example, high dosages of aspirin are administered to mammalian subjects in the treatment of inflammatory conditions associated with diseases generally described as rheumatic or arthritic types, but attendant to the beneficial effects of reduction of inflammation and swelling of joints and tissue in various parts of the mammalian body are detrimental effects of ulceration and bleeding with appreciable blood loss in the stomach. The need to overcome these side effects due to aspirin administration is well recognized in the fields of human and veterinary medicine and that in some cases the continual loss of blood cannot be tolerated. Oftentimes, aspirin therapy must be terminated, thus giving rise to exposure, in the search for other satisfactory chemotherapy, to the potential danger from certain other anti-inflammatory agents which may cause even more severe ulceration and perforation in certain parts of the gastrointestinal tract. Thus, the accomplishment of the present invention in reducing bleeding due to aspirin therapy can be readily appreciated by one skilled in the art, particularly when it is realized that conditions of intolerance to aspirin because of induced ulceration and bleeding can be avoided by the methods, combinations and compositions of this invention.
Indicative of the state of the art have been attempts to find combinations which would allow administration of aspirin for its full therapeutic effect as an anti-inflammatory drug. Coprecipitates of aspirin with lignosulfonate (Brit. Pat. No. 1,345,358) with tannic acid (Brit. Pat. No. 1,345,359) and tea (Belg. Pat. No. 806,392) have all shown reduced irritation in the cat stomach.
Cyclobenzaprine combined with aspirin for muscle relaxing effect in animals has been disclosed in British Pat. No. 1,334,326. The dosages of both cyclobenzaprine and aspirin are said to be subclinical and because less of these drugs is used, side effects are reduced. In the instant invention aspirin is administered in full dosage amount for its anti-inflammatory effect and the phenylalkylamines or phenylalkylureas are co-administered to reduce the bleeding normally attendant to full dosage amounts of aspirin.